However, the role of RhoA in regulating carcinogenesis is controversial since it is unclear whether RhoA mutation is loss-of -function or gain-of-function.494 The aberrations of CDH1, RHOA, and CLDN18-ARHGAP26 are enriched in the GS subset of GC according to TCGA.41 Understanding the crosstalk of these three gene aberrations will be key to revealing the mechanisms leading to tumorigenesis in diffused GC. This evidence concerns the gene CLDN18 and gastric cancer.